Serum IgG4 elevation in pancreatic cancer: surgery and prognostic significance_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

PEI Jinyu , LIU Peng , CAO Guanghua , WANG Jing , MA Xiang ,  QU Linlin

Department of Hepatobiliary Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P. R. China;

Corresponding author：

QU Linlin, Email: taxue9455@sina.com

Keywords：

serum IgG4; pancreatic cancer; autoimmune pancreatitis; prognosis; survival time

DOI：

10.7507/1007-9424.202008104

Video：

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Objective To analyze the R0 resection rate and survival time of pancreatic cancer with serum IgG4 elevated, and to discuss whether serum IgG4 can distinguish autoimmune pancreatitis from pancreatic cancer.Methods The retrospective cohort study was adopted. The clinical data of 146 patients with pancreatic cancer confirmed by histology in Affiliated Hospital of Qingdao University from January 2016 to December 2019 were analyzed retrospectively. According to the level of serum IgG4, they were divided into normal IgG4 group (<1.35 g/L, n=124) and IgG4 elevated group (≥1.35 g/L, n=22). The tumor R0 resection rate, survival time and whether complicated with AIP of the two groups were compared.Results One hundred and one patients (81.5%) with normal serum IgG4 underwent radical surgery, while only 13 patients (59.1%) with elevated serum IgG4 underwent radical surgery, the difference was significant (P=0.019). The median survival time of patients with normal serum IgG4 was 18.7 months, while patients with elevated serum IgG4 was 8.1 months, there was no significant difference between the two groups (P=0.121). Subgroup analysis showed that the median survival time of patients with pancreatic ductal adenocarcinoma in the normal IgG4 group was 17.5 months, while the IgG4 elevated group was 6.8 months, the difference was significant (P=0.016). Only 1 case of pancreatic cancer with AIP in the 2 groups.Conclusions Serum IgG4 ≥1.35 g/L indicates low radical resection rate in pancreatic cancer and poor prognosis in pancreatic ductal adenocarcinoma. Serum IgG4 can only be used as an auxiliary index to distinguish pancreatic cancer from autoimmune pancreatitis.

Citation： PEI Jinyu, LIU Peng, CAO Guanghua, WANG Jing, MA Xiang, QU Linlin. Serum IgG4 elevation in pancreatic cancer: surgery and prognostic significance. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(6): 774-778. doi: 10.7507/1007-9424.202008104 Copy

1.	Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin, 2019, 69(1): 7-34.
2.	Riker A, Libutti SK, Bartlett DL. Advances in the early detection, diagnosis, and staging of pancreatic cancer. Surg Oncol, 1997, 6(3): 157-169.
3.	Deshpande V, Chicano S, Finkelberg D, et al. Autoimmune pancreatitis: a systemic immune complex mediated disease. Am J Surg Pathol, 2006, 30(12): 1537-1545.
4.	Kamisawa T, Egawa N, Nakajima H, et al. Clinical difficulties in the differentiation of autoimmune pancreatitis and pancreatic carcinoma. Am J Gastroenterol, 2003, 98(12): 2694-2699.
5.	Chari ST, Takahashi N, Levy MJ, et al. A diagnostic strategy to distinguish autoimmune pancreatitis from pancreatic cancer. Clin Gastroenterol Hepatol, 2009, 7(10): 1097-1103.
6.	He C, Rong D, Hu W, et al. A feasible CT feature to differentiate focal-type autoimmune pancreatitis from pancreatic ductal adenocarcinoma. Cancer Med, 2019, 8(14): 6250-6257.
7.	Okazaki K, Kawa S, Kamisawa T, et al. Amendment of the Japanese Consensus Guidelines for Autoimmune Pancreatitis, 2013 I. Concept and diagnosis of autoimmune pancreatitis. J Gastroenterol, 2014, 49(4): 567-588.
8.	Hamano H, Kawa S, Horiuchi A, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med, 2001, 344(10): 732-738.
9.	Choi EK, Kim MH, Lee TY, et al. The sensitivity and specificity of serum immunoglobulin G and immunoglobulin G4 levels in the diagnosis of autoimmune chronic pancreatitis: Korean experience. Pancreas, 2007, 35(2): 156-161.
10.	Okazaki K, Kawa S, Kamisawa T, et al. Clinical diagnostic criteria of autoimmune pancreatitis: revised proposal. J Gastroenterol, 2006, 41(7): 626-631.
11.	Maruyama M, Watanabe T, Kanai K, et al. International consensus diagnostic criteria for autoimmune pancreatitis and its Japanese amendment have improved diagnostic ability over existing criteria. Gastroenterol Res Pract, 2013, 2013: 456965.
12.	Raina A, Krasinskas AM, Greer JB, et al. Serum immunoglobulin G fraction 4 levels in pancreatic cancer: elevations not associated with autoimmune pancreatitis. Arch Pathol Lab Med, 2008, 132(1): 48-53.
13.	Ghazale A, Chari ST, Smyrk TC, et al. Value of serum IgG4 in the diagnosis of autoimmune pancreatitis and in distinguishing it from pancreatic cancer. Am J Gastroenterol, 2007, 102(8): 1646-1653.
14.	Yoshida K, Toki F, Takeuchi T, et al. Chronic pancreatitis caused by an autoimmune abnormality. Proposal of the concept of autoimmune pancreatitis. Dig Dis Sci, 1995, 40(7): 1561-1568.
15.	Kamisawa T, Imai M, Yui Chen P, et al. Strategy for differentiating autoimmune pancreatitis from pancreatic cancer. Pancreas, 2008, 37(3): e62-e67.
16.	Chang MC, Liang PC, Jan S, et al. Increase diagnostic accuracy in differentiating focal type autoimmune pancreatitis from pancreatic cancer with combined serum IgG4 and CA19-9 levels. Pancreatology, 2014, 14(5): 366-372.
17.	Pak LM, Schattner MA, Balachandran V, et al. The clinical utility of immunoglobulin G4 in the evaluation of autoimmune pancreatitis and pancreatic adenocarcinoma. HPB (Oxford), 2018, 20(2): 182-187.
18.	Bojková M, Dítě P, Dvořáčková J, et al. Immunoglobulin G4, autoimmune pancreatitis and pancreatic cancer. Dig Dis, 2015, 33(1): 86-90.
19.	Dite P, Novotny I, Dvorackova J, et al. Pancreatic solid focal lesions: differential diagnosis between autoimmune pancreatitis and pancreatic cancer. Dig Dis, 2019, 37(5): 416-421.
20.	Dickerson LD, Farooq A, Bano F, et al. Differentiation of autoimmune pancreatitis from pancreatic cancer remains challenging. World J Surg, 2019, 43(6): 1604-1611.
21.	Ngwa T, Law R, Hart P, et al. Serum IgG4 elevation in pancreatic cancer: diagnostic and prognostic significance and association with autoimmune pancreatitis. Pancreas, 2015, 44(4): 557-560.
22.	Liu Q, Niu Z, Li Y, et al. Immunoglobulin G4(IgG4)-positive plasma cell infiltration is associated with the clinicopathologic traits and prognosis of pancreatic cancer after curative resection. Cancer Immunol Immunother, 2016, 65(8): 931-940.
23.	Karagiannis P, Gilbert AE, Nestle FO, et al. IgG4 antibodies and cancer-associated inflammation: Insights into a novel mechanism of immune escape. Oncoimmunology, 2013, 2(7): e24889.

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin, 2019, 69(1): 7-34.
2. Riker A, Libutti SK, Bartlett DL. Advances in the early detection, diagnosis, and staging of pancreatic cancer. Surg Oncol, 1997, 6(3): 157-169.
3. Deshpande V, Chicano S, Finkelberg D, et al. Autoimmune pancreatitis: a systemic immune complex mediated disease. Am J Surg Pathol, 2006, 30(12): 1537-1545.
4. Kamisawa T, Egawa N, Nakajima H, et al. Clinical difficulties in the differentiation of autoimmune pancreatitis and pancreatic carcinoma. Am J Gastroenterol, 2003, 98(12): 2694-2699.
5. Chari ST, Takahashi N, Levy MJ, et al. A diagnostic strategy to distinguish autoimmune pancreatitis from pancreatic cancer. Clin Gastroenterol Hepatol, 2009, 7(10): 1097-1103.
6. He C, Rong D, Hu W, et al. A feasible CT feature to differentiate focal-type autoimmune pancreatitis from pancreatic ductal adenocarcinoma. Cancer Med, 2019, 8(14): 6250-6257.
7. Okazaki K, Kawa S, Kamisawa T, et al. Amendment of the Japanese Consensus Guidelines for Autoimmune Pancreatitis, 2013 I. Concept and diagnosis of autoimmune pancreatitis. J Gastroenterol, 2014, 49(4): 567-588.
8. Hamano H, Kawa S, Horiuchi A, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med, 2001, 344(10): 732-738.
9. Choi EK, Kim MH, Lee TY, et al. The sensitivity and specificity of serum immunoglobulin G and immunoglobulin G4 levels in the diagnosis of autoimmune chronic pancreatitis: Korean experience. Pancreas, 2007, 35(2): 156-161.
10. Okazaki K, Kawa S, Kamisawa T, et al. Clinical diagnostic criteria of autoimmune pancreatitis: revised proposal. J Gastroenterol, 2006, 41(7): 626-631.
11. Maruyama M, Watanabe T, Kanai K, et al. International consensus diagnostic criteria for autoimmune pancreatitis and its Japanese amendment have improved diagnostic ability over existing criteria. Gastroenterol Res Pract, 2013, 2013: 456965.
12. Raina A, Krasinskas AM, Greer JB, et al. Serum immunoglobulin G fraction 4 levels in pancreatic cancer: elevations not associated with autoimmune pancreatitis. Arch Pathol Lab Med, 2008, 132(1): 48-53.
13. Ghazale A, Chari ST, Smyrk TC, et al. Value of serum IgG4 in the diagnosis of autoimmune pancreatitis and in distinguishing it from pancreatic cancer. Am J Gastroenterol, 2007, 102(8): 1646-1653.
14. Yoshida K, Toki F, Takeuchi T, et al. Chronic pancreatitis caused by an autoimmune abnormality. Proposal of the concept of autoimmune pancreatitis. Dig Dis Sci, 1995, 40(7): 1561-1568.
15. Kamisawa T, Imai M, Yui Chen P, et al. Strategy for differentiating autoimmune pancreatitis from pancreatic cancer. Pancreas, 2008, 37(3): e62-e67.
16. Chang MC, Liang PC, Jan S, et al. Increase diagnostic accuracy in differentiating focal type autoimmune pancreatitis from pancreatic cancer with combined serum IgG4 and CA19-9 levels. Pancreatology, 2014, 14(5): 366-372.
17. Pak LM, Schattner MA, Balachandran V, et al. The clinical utility of immunoglobulin G4 in the evaluation of autoimmune pancreatitis and pancreatic adenocarcinoma. HPB (Oxford), 2018, 20(2): 182-187.
18. Bojková M, Dítě P, Dvořáčková J, et al. Immunoglobulin G4, autoimmune pancreatitis and pancreatic cancer. Dig Dis, 2015, 33(1): 86-90.
19. Dite P, Novotny I, Dvorackova J, et al. Pancreatic solid focal lesions: differential diagnosis between autoimmune pancreatitis and pancreatic cancer. Dig Dis, 2019, 37(5): 416-421.
20. Dickerson LD, Farooq A, Bano F, et al. Differentiation of autoimmune pancreatitis from pancreatic cancer remains challenging. World J Surg, 2019, 43(6): 1604-1611.
21. Ngwa T, Law R, Hart P, et al. Serum IgG4 elevation in pancreatic cancer: diagnostic and prognostic significance and association with autoimmune pancreatitis. Pancreas, 2015, 44(4): 557-560.
22. Liu Q, Niu Z, Li Y, et al. Immunoglobulin G4(IgG4)-positive plasma cell infiltration is associated with the clinicopathologic traits and prognosis of pancreatic cancer after curative resection. Cancer Immunol Immunother, 2016, 65(8): 931-940.
23. Karagiannis P, Gilbert AE, Nestle FO, et al. IgG4 antibodies and cancer-associated inflammation: Insights into a novel mechanism of immune escape. Oncoimmunology, 2013, 2(7): e24889.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Serum IgG4 elevation in pancreatic cancer: surgery and prognostic significance

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